CACUL1/CAC1 attenuates p53 activity through PML post-translational modification.
CACUL1/CAC1 attenuates p53 activity through PML post-translational modification.
复制标题
DOI：
10.1016/j.bbrc.2016.11.125
复制
发表时间：
2017-01
影响因子：
3.1
通讯作者：
Tomomi Fukuda;Yu Kigoshi-Tansho;T. Naganuma;Akira Kazaana;Tomomi Okajima;Fuminori Tsuruta;T. Chiba
中科院分区：
文献类型：
--
作者：
Tomomi Fukuda;Yu Kigoshi-Tansho;T. Naganuma;Akira Kazaana;Tomomi Okajima;Fuminori Tsuruta;T. Chiba
早幼粒细胞白血病（PML）是一种与SUMO家族蛋白共价结合的肿瘤抑制蛋白，导致PML核体（NB）的形成。PML-NB为靶点的有效翻译后修饰和蛋白质-蛋白质相互作用提供了一个平台，有助于基因表达和染色质完整性的调节。尽管PML SUMO化被认为在多种细胞功能中发挥重要作用，但适当修饰水平的控制机制仍然没有解决。在这里，我们报告，Cullin相关蛋白CACUL 1/CAC 1（CACUL 1）抑制PML翻译后修饰。CACUL 1与PML相互作用并抑制PML SUMO化，导致细胞核中PML-NB大小的调节。我们还发现，Ubc 9，SUMO结合酶，结合到CACUL 1和拮抗CACUL 1和PML之间的相互作用。此外，CACUL 1减弱p53转录活性。这些数据表明，CACUL 1是一种新的调节剂，通过调节PML SUMO化负控制p53活性。
Promyelocytic leukaemia (PML) is a tumor suppressor protein covalently conjugated with SUMO family proteins, leading to the formation of PML nuclear bodies (NBs). PML-NBs provide a platform for efficient posttranslational modification of targets and protein-protein interaction, contributing to the adjustment of gene expression and chromatin integrity. Although PML SUMOylation is thought to play important roles in diverse cellular functions, the control mechanisms of adequate modification levels have remained unsolved. Here, we report that Cullin-related protein CACUL1/CAC1 (CACUL1) inhibits PML posttranslational modification. CACUL1 interacts with PML and suppresses PML SUMOylation, leading to the regulation of PML-NB size in the nucleus. We also found that Ubc9, a SUMO-conjugating enzyme, binds to CACUL1 and antagonizes the interaction between CACUL1 and PML. Furthermore, CACUL1 attenuates p53 transcriptional activity. These data suggest that CACUL1 is a novel regulator that negatively controls p53 activity through the regulation of PML SUMOylation.